The overall goal is to integrate advances in technological development of physiologic neuro-imaging and tissue biomarkers in the management of patients with brain tumors and to translate this knowledge to optimize treatment. Malignant glioma is a significant clinical challenge and much effort is expended in the development of new therapeutic strategies. Although radiation therapy (XRT) prolongs survival for glioblastoma multiforme (GBM), about 30 percent of patients progress during the course of XRT and have a poor prognosis. Project 1 will study the potential of metabolic and physiologic imaging and tissue correlates to identify these patients prior to initiation of therapy and to integrate this knowledge in an individualized treatment paradigm. Patients with GBM universally progress and these recurrent tumors are heterogeneous in their behavior. Apart from patient-related prognostic factors (age and performance status), there are no biological predictors of outcome. Project 2 will study the non-invasive physiologic and metabolic parameters with tissue correlates to better understand tumor heterogeneity and biological behavior. This information should have a major impact on the selection of patients for clinical trials and the design and interpretation of results. If the physiologic imaging parameters are indeed representative of biological behavior such as angiogenesis or invasive capacity, this will have significant application in the evaluation of novel targeted therapies. New therapeutic approaches involve the interstitial delivery of agents into tumor-infiltrated brain parenchyma. Determining the extent and nature of the invasive component of infiltrative tumor is limited with standard imaging. Project 3 will study the non-invasive real-time imaging of interstitial administration of agents in animals and non-human primates to define the target for infusion and optimize delivery of therapeutic agents. The Clinical Services Core and Imaging and Tissue Correlate Core will provide services to all projects to centralize the effort for efficient and integrated management of this program project grant.